Trial Outcomes & Findings for A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate Versus RoActemra/Actemra Monotherapy in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate (NCT NCT01399697)
NCT ID: NCT01399697
Last Updated: 2015-07-13
Results Overview
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (erythrocyte sedimentation rate \[ESR\] in millimeters per hour \[mm/hr\]), and general health status (participant global assessment of disease activity using visual analog scale \[VAS\], range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
261 participants
Primary outcome timeframe
Baseline, Week 16, and Week 28
Results posted on
2015-07-13
Participant Flow
Participant milestones
| Measure |
Tocilizumab (TCZ) Plus (+) Methotrexate (Not Randomized)
Participants received TCZ 8 milligrams per kilogram (mg/kg; maximum 800 mg) via intravenous (IV) infusion every 4 weeks (q4w) through Week 24 (total of 7 infusions). Participants also received methotrexate (MTX) capsules orally, at a stable dose (10, 15, 17.5, or 20 mg, no maximum dose was defined) weekly from Week 1 through 16.
|
TCZ + MTX (Randomized)
Participants received TCZ 8 mg/kg (maximum 800 mg) via IV infusion q4w through Week 24 (total of 7 infusions). Participants also received MTX capsules, orally, at a stable dose (10, 15, 17.5, or 20 mg/week, but no maximum dose was defined), weekly, from Weeks 1 through 24.
|
TCZ + Placebo (Randomized)
Participants received TCZ 8 mg/kg (maximum 800 mg) via IV infusion q4w through Week 24 (total of 7 infusions). Participants also received MTX capsules, orally, at stable dose (10, 15, 17.5, or 20 mg per week, but no maximum dose was defined) weekly, from Weeks 1 through 16 followed by matching placebo capsules, orally, weekly through Week 24.
|
|---|---|---|---|
|
Overall Study
STARTED
|
96
|
83
|
82
|
|
Overall Study
COMPLETED
|
55
|
80
|
78
|
|
Overall Study
NOT COMPLETED
|
41
|
3
|
4
|
Reasons for withdrawal
| Measure |
Tocilizumab (TCZ) Plus (+) Methotrexate (Not Randomized)
Participants received TCZ 8 milligrams per kilogram (mg/kg; maximum 800 mg) via intravenous (IV) infusion every 4 weeks (q4w) through Week 24 (total of 7 infusions). Participants also received methotrexate (MTX) capsules orally, at a stable dose (10, 15, 17.5, or 20 mg, no maximum dose was defined) weekly from Week 1 through 16.
|
TCZ + MTX (Randomized)
Participants received TCZ 8 mg/kg (maximum 800 mg) via IV infusion q4w through Week 24 (total of 7 infusions). Participants also received MTX capsules, orally, at a stable dose (10, 15, 17.5, or 20 mg/week, but no maximum dose was defined), weekly, from Weeks 1 through 24.
|
TCZ + Placebo (Randomized)
Participants received TCZ 8 mg/kg (maximum 800 mg) via IV infusion q4w through Week 24 (total of 7 infusions). Participants also received MTX capsules, orally, at stable dose (10, 15, 17.5, or 20 mg per week, but no maximum dose was defined) weekly, from Weeks 1 through 16 followed by matching placebo capsules, orally, weekly through Week 24.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
13
|
3
|
1
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
8
|
0
|
0
|
|
Overall Study
Investigator Decisión
|
1
|
0
|
2
|
|
Overall Study
Lack of Efficacy
|
9
|
0
|
1
|
|
Overall Study
Protocol Violation
|
2
|
0
|
0
|
|
Overall Study
Non-Compliant
|
1
|
0
|
0
|
|
Overall Study
Inclusion Error
|
2
|
0
|
0
|
|
Overall Study
Positive result for hepatitis B
|
1
|
0
|
0
|
|
Overall Study
Clinical RA remission
|
1
|
0
|
0
|
|
Overall Study
Sponsor Decision
|
1
|
0
|
0
|
Baseline Characteristics
A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate Versus RoActemra/Actemra Monotherapy in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate
Baseline characteristics by cohort
| Measure |
TCZ + MTX (Not Randomized)
n=96 Participants
Participants received TCZ 8 mg/kg (maximum 800 mg) via IV infusion q4w through Week 24 (total of 7 infusions). Participants also received MTX capsules orally, at a stable dose (10, 15, 17.5, or 20 mg, no maximum dose was defined) weekly from Week 1 through 16.
|
TCZ + MTX (Randomized)
n=83 Participants
Participants received TCZ 8 mg/kg (maximum 800 mg) via IV infusion q4w through Week 24 (total of 7 infusions). Participants also received MTX capsules, orally, at a stable dose (10, 15, 17.5, or 20 mg/week, but no maximum dose was defined), weekly, from Weeks 1 through 24.
|
TCZ + Placebo (Randomized)
n=82 Participants
Participants received TCZ 8 mg/kg (maximum 800 mg) via IV infusion q4w through Week 24 (total of 7 infusions). Participants also received MTX capsules, orally, at stable dose (10, 15, 17.5, or 20 mg per week, but no maximum dose was defined) weekly, from Weeks 1 through 16 followed by matching placebo capsules, orally, weekly through Week 24.
|
Total
n=261 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
52.3 years
STANDARD_DEVIATION 13.2 • n=5 Participants
|
50.2 years
STANDARD_DEVIATION 12.5 • n=7 Participants
|
51.0 years
STANDARD_DEVIATION 12.2 • n=5 Participants
|
51.2 years
STANDARD_DEVIATION 12.6 • n=4 Participants
|
|
Sex: Female, Male
Female
|
76 Participants
n=5 Participants
|
62 Participants
n=7 Participants
|
65 Participants
n=5 Participants
|
203 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
58 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 16, and Week 28Population: Intent-to-treat (ITT) population: all randomized participants who received at least one dose of study medication and who had at least one efficacy measurement performed.
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (erythrocyte sedimentation rate \[ESR\] in millimeters per hour \[mm/hr\]), and general health status (participant global assessment of disease activity using visual analog scale \[VAS\], range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Outcome measures
| Measure |
TCZ + MTX (Randomized)
n=83 Participants
TCZ 8 mg/kg (maximum 800 mg) IV q4w along with MTX orally at a stable dose (10, 15, 17.5 or 20 mg/week) up to Week 28.
|
TCZ + Placebo (Randomized)
n=82 Participants
TCZ 8 mg/kg (maximum 800 mg) q4w IV up to Week 28 along with MTX orally at stable dose (10, 15, 17.5 or 20 mg per week) up to Week 16 followed by placebo matched to MTX along with TCZ up to Week 28.
|
|---|---|---|
|
Change in Disease Activity Score Based on 28-Joint Count (DAS28) From Week 16 to Week 28
Baseline
|
5.42 units on a scale
Standard Deviation 1.01
|
5.29 units on a scale
Standard Deviation 1.01
|
|
Change in Disease Activity Score Based on 28-Joint Count (DAS28) From Week 16 to Week 28
Week 16
|
1.77 units on a scale
Standard Deviation 0.77
|
1.96 units on a scale
Standard Deviation 0.76
|
|
Change in Disease Activity Score Based on 28-Joint Count (DAS28) From Week 16 to Week 28
Week 28
|
1.82 units on a scale
Standard Deviation 1.18
|
1.98 units on a scale
Standard Deviation 1.13
|
SECONDARY outcome
Timeframe: Week 28Population: ITT Population; only participants with Week 28 DAS28 values were included in the analysis.
The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores indicate worsening. DAS28 \<2.6 equals (=) remission.
Outcome measures
| Measure |
TCZ + MTX (Randomized)
n=79 Participants
TCZ 8 mg/kg (maximum 800 mg) IV q4w along with MTX orally at a stable dose (10, 15, 17.5 or 20 mg/week) up to Week 28.
|
TCZ + Placebo (Randomized)
n=79 Participants
TCZ 8 mg/kg (maximum 800 mg) q4w IV up to Week 28 along with MTX orally at stable dose (10, 15, 17.5 or 20 mg per week) up to Week 16 followed by placebo matched to MTX along with TCZ up to Week 28.
|
|---|---|---|
|
Percentage of Participants With DAS28 Score Less Than (<) 2.6 at Week 28
|
82.3 percentage of participants
|
75.9 percentage of participants
|
SECONDARY outcome
Timeframe: Week 28Population: ITT Population; only participants with CDAI scores at Weeks 28 were included in the analysis.
CDAI is the sum of tender and swollen joint count based on 28 joints and the participant and physician global disease assessment (VAS 0-10 centimeters \[cm\]). CDAI total score 0-76; higher scores = greater affect due to disease activity. CDAI \<2.8 = clinical remission.
Outcome measures
| Measure |
TCZ + MTX (Randomized)
n=81 Participants
TCZ 8 mg/kg (maximum 800 mg) IV q4w along with MTX orally at a stable dose (10, 15, 17.5 or 20 mg/week) up to Week 28.
|
TCZ + Placebo (Randomized)
n=81 Participants
TCZ 8 mg/kg (maximum 800 mg) q4w IV up to Week 28 along with MTX orally at stable dose (10, 15, 17.5 or 20 mg per week) up to Week 16 followed by placebo matched to MTX along with TCZ up to Week 28.
|
|---|---|---|
|
Percentage of Participants With Clinical Disease Activity Index (CDAI) <2.8 at Week 28
|
40.7 percentage of participants
|
35.8 percentage of participants
|
SECONDARY outcome
Timeframe: 28 weeksPopulation: ITT Population; only participants with SDAI scores at Week 28 were included in the analysis.
SDAI is calculated by a simple numerical sum of tender and swollen joint count (based on a 28-joint assessment), participant and physician global assessment of disease activity (VAS 0-10 cm), and level of C-reactive protein in milligram per deciliter (mg/dL). SDAI total score 0-86; higher scores = greater affect due to disease activity. SDAI \<3.3 = clinical remission.
Outcome measures
| Measure |
TCZ + MTX (Randomized)
n=77 Participants
TCZ 8 mg/kg (maximum 800 mg) IV q4w along with MTX orally at a stable dose (10, 15, 17.5 or 20 mg/week) up to Week 28.
|
TCZ + Placebo (Randomized)
n=78 Participants
TCZ 8 mg/kg (maximum 800 mg) q4w IV up to Week 28 along with MTX orally at stable dose (10, 15, 17.5 or 20 mg per week) up to Week 16 followed by placebo matched to MTX along with TCZ up to Week 28.
|
|---|---|---|
|
Percentage of Participants With Simplified Disease Activity Index (SDAI) <3.3 at Week 28
|
35.1 percentage of participants
|
28.2 percentage of participants
|
SECONDARY outcome
Timeframe: Week 16 and Week 28Population: ITT Population; only participants with non missing values were included in the analysis.
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Outcome measures
| Measure |
TCZ + MTX (Randomized)
n=80 Participants
TCZ 8 mg/kg (maximum 800 mg) IV q4w along with MTX orally at a stable dose (10, 15, 17.5 or 20 mg/week) up to Week 28.
|
TCZ + Placebo (Randomized)
n=82 Participants
TCZ 8 mg/kg (maximum 800 mg) q4w IV up to Week 28 along with MTX orally at stable dose (10, 15, 17.5 or 20 mg per week) up to Week 16 followed by placebo matched to MTX along with TCZ up to Week 28.
|
|---|---|---|
|
Change in the Health Assessment Questionnaire Disability Index (HAQ-DI) From Week 16 to Week 28
|
0.08 units on a scale
Standard Deviation 0.47
|
0.00 units on a scale
Standard Deviation 0.52
|
SECONDARY outcome
Timeframe: Week 16 and Week 28Population: ITT Population; only participants with non missing values were included in the analysis.
Quality of life questionnaire (SF-12) scores were computed using the scores of 12 questions and ranged from 0 to 100, where a 0 score indicated the lowest level of health measured by the scales and 100 indicated the highest level of health. A negative change from baseline indicated decline in health and higher scores indicated improvement in health.
Outcome measures
| Measure |
TCZ + MTX (Randomized)
n=79 Participants
TCZ 8 mg/kg (maximum 800 mg) IV q4w along with MTX orally at a stable dose (10, 15, 17.5 or 20 mg/week) up to Week 28.
|
TCZ + Placebo (Randomized)
n=79 Participants
TCZ 8 mg/kg (maximum 800 mg) q4w IV up to Week 28 along with MTX orally at stable dose (10, 15, 17.5 or 20 mg per week) up to Week 16 followed by placebo matched to MTX along with TCZ up to Week 28.
|
|---|---|---|
|
Change in the Quality of Life Questionnaire (Short Form-12 [SF-12]) From Week 16 to Week 28 in Mental Health
|
-2.36 units on a scale
Standard Deviation 10.22
|
-0.38 units on a scale
Standard Deviation 9.25
|
SECONDARY outcome
Timeframe: Week 16 and Week 28Population: ITT Population; only participants with non missing data were included in the analysis.
Quality of life questionnaire (SF-12) scores were computed using the scores of 12 questions and ranged from 0 to 100, where a 0 score indicated the lowest level of health measured by the scales and 100 indicated the highest level of health. A negative change from baseline indicated a worsening of quality of life.
Outcome measures
| Measure |
TCZ + MTX (Randomized)
n=79 Participants
TCZ 8 mg/kg (maximum 800 mg) IV q4w along with MTX orally at a stable dose (10, 15, 17.5 or 20 mg/week) up to Week 28.
|
TCZ + Placebo (Randomized)
n=79 Participants
TCZ 8 mg/kg (maximum 800 mg) q4w IV up to Week 28 along with MTX orally at stable dose (10, 15, 17.5 or 20 mg per week) up to Week 16 followed by placebo matched to MTX along with TCZ up to Week 28.
|
|---|---|---|
|
Change in the Quality of Life Questionnaire (SF-12) From Week 16 to Week 28 in Physical Health
|
0.48 units on a scale
Standard Deviation 9.49
|
-2.26 units on a scale
Standard Deviation 8.82
|
SECONDARY outcome
Timeframe: Week 16 and Week 28Population: ITT Population; only participants with non missing values were included in the analysis.
Participants were asked to rate their global assessment of disease activity on a scale ranging from 0=very good to 100=very bad. The scale was represented by a line with 0 at the left edge and 100 at the right edge. The participant was asked to mark the line corresponding to the assessment of their disease activity. The distance from the left edge was measured in mm.
Outcome measures
| Measure |
TCZ + MTX (Randomized)
n=82 Participants
TCZ 8 mg/kg (maximum 800 mg) IV q4w along with MTX orally at a stable dose (10, 15, 17.5 or 20 mg/week) up to Week 28.
|
TCZ + Placebo (Randomized)
n=82 Participants
TCZ 8 mg/kg (maximum 800 mg) q4w IV up to Week 28 along with MTX orally at stable dose (10, 15, 17.5 or 20 mg per week) up to Week 16 followed by placebo matched to MTX along with TCZ up to Week 28.
|
|---|---|---|
|
Change From Week 16 to Week 28 in Global Assessment of Disease Activity as Assessed With the Visual Analogue Scale (VAS) Performed by Participant
|
1.68 units on a scale
Standard Deviation 23.80
|
0.56 units on a scale
Standard Deviation 20.42
|
SECONDARY outcome
Timeframe: Week 16 and Week 28Population: ITT Population; only participants with non missing values were included in the analysis.
Participants were asked to rate their global assessment of disease activity on a scale ranging from 0=very good to 100=very bad. The scale was represented by a line with 0 at the left edge and 100 at the right edge. The participant was asked to mark the line corresponding to the assessment of their disease activity. The distance from the left edge was measured in mm.
Outcome measures
| Measure |
TCZ + MTX (Randomized)
n=82 Participants
TCZ 8 mg/kg (maximum 800 mg) IV q4w along with MTX orally at a stable dose (10, 15, 17.5 or 20 mg/week) up to Week 28.
|
TCZ + Placebo (Randomized)
n=81 Participants
TCZ 8 mg/kg (maximum 800 mg) q4w IV up to Week 28 along with MTX orally at stable dose (10, 15, 17.5 or 20 mg per week) up to Week 16 followed by placebo matched to MTX along with TCZ up to Week 28.
|
|---|---|---|
|
Change From Week 16 to Week 28 in Global Assessment of Disease Activity Assessed Using the VAS Performed by the Investigator
|
2.71 units on a scale
Standard Deviation 16.96
|
2.85 units on a scale
Standard Deviation 18.48
|
Adverse Events
TCZ + MTX (Not Randomized)
Serious events: 11 serious events
Other events: 28 other events
Deaths: 0 deaths
TCZ + MTX (Pre-randomization)
Serious events: 0 serious events
Other events: 20 other events
Deaths: 0 deaths
TCZ + Placebo (Pre-randomization)
Serious events: 1 serious events
Other events: 24 other events
Deaths: 0 deaths
TCZ + MTX (Post-randomization)
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
TCZ + Placebo (Post-randomization)
Serious events: 4 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TCZ + MTX (Not Randomized)
n=96 participants at risk
Participants received TCZ 8 mg/kg (maximum 800 mg) via IV infusion q4w through Week 24 (total of 7 infusions). Participants also received MTX capsules orally, at a stable dose (10, 15, 17.5, or 20 mg, no maximum dose was defined) weekly from Week 1 through 16.
|
TCZ + MTX (Pre-randomization)
n=83 participants at risk
Participants received TCZ 8 mg/kg (maximum 800 mg) via IV infusion q4w up to Week 16 (total of 4 infusions). Participants also received MTX capsules, orally at a stable dose (10, 15, 17.5, or 20 mg/week but no maximum dose was set) weekly, up to Week 16. Participants with a response were randomized to receive TCZ and MTX in the second part of the study. Response was defined as participants having DAS28 score less than or equal to (\<=)3.2.
|
TCZ + Placebo (Pre-randomization)
n=82 participants at risk
Participants received TCZ 8 mg/kg (maximum 800 mg) via IV infusion q4w up to Week 16 (total of 4 infusions). Participants also received MTX capsules, orally at a stable dose (10, 15, 17.5, or 20 mg/week but no maximum dose was set) weekly, up to Week 16. Participants with a response were randomized to receive TCZ and matching MTX placebo in the second part of the study. Response was defined as participants having DAS28 score \<=3.2.
|
TCZ + MTX (Post-randomization)
n=83 participants at risk
TCZ 8 mg/kg (maximum 800 mg) q4w via IV infusion up to Week 16 (total of 4 infusions). Participants also received MTX capsules, orally, at a stable dose (10, 15, 17.5, or 20 mg/week but no maximum dose was set) weekly, up to Week 16. Participants with a response were randomized to receive 3 additional IV infusions of TCZ 8 mg/kg between Week 16 and Week 24 and MTX capsules, orally, at a stable dose (10, 15, 17.5, or 20 mg per week, but no maximum dose was set), weekly through Week 24. Response was defined as participants having DAS28 score \<=3.2.
|
TCZ + Placebo (Post-randomization)
n=82 participants at risk
TCZ 8 mg/kg (maximum 800 mg) q4w via IV infusion up to Week 16 (total of 4 infusions). Participants also received MTX capsules, orally, at a stable dose (10, 15, 17.5, or 20 mg/week but no maximum dose was set) weekly, up to Week 16. Participants with a response were randomized to receive 3 additional IV infusions of TCZ 8 mg/kg between Week 16 and Week 24 and matching placebo MTX capsules, orally, at a stable dose (10, 15, 17.5, or 20 mg per week, but no maximum dose was set), weekly through Week 24. Response was defined as participants having DAS28 score \<=3.2.
|
|---|---|---|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
1.2%
1/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
General disorders
Chest Pain
|
1.0%
1/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Hepatobiliary disorders
Hypertransaminasaemia
|
3.1%
3/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Infections and infestations
Bursitis infective
|
0.00%
0/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
1.2%
1/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Infections and infestations
Endocarditis bacterial
|
0.00%
0/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
1.2%
1/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Infections and infestations
Pneumonia
|
1.0%
1/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
1.2%
1/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Infections and infestations
Staphylococcal skin infection
|
0.00%
0/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
1.2%
1/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Infections and infestations
Cytomegalovirus infection
|
1.0%
1/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Infections and infestations
Herpes zoster
|
1.0%
1/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Infections and infestations
Pyelonephritis acute
|
1.0%
1/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Infections and infestations
Salpingitis
|
1.0%
1/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
1.0%
1/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Musculoskeletal and connective tissue disorders
Lupus-like syndrome
|
1.0%
1/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Nervous system disorders
Epilepsy
|
1.0%
1/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Vascular disorders
Deep vein thrombosis
|
2.1%
2/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
1.2%
1/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
Other adverse events
| Measure |
TCZ + MTX (Not Randomized)
n=96 participants at risk
Participants received TCZ 8 mg/kg (maximum 800 mg) via IV infusion q4w through Week 24 (total of 7 infusions). Participants also received MTX capsules orally, at a stable dose (10, 15, 17.5, or 20 mg, no maximum dose was defined) weekly from Week 1 through 16.
|
TCZ + MTX (Pre-randomization)
n=83 participants at risk
Participants received TCZ 8 mg/kg (maximum 800 mg) via IV infusion q4w up to Week 16 (total of 4 infusions). Participants also received MTX capsules, orally at a stable dose (10, 15, 17.5, or 20 mg/week but no maximum dose was set) weekly, up to Week 16. Participants with a response were randomized to receive TCZ and MTX in the second part of the study. Response was defined as participants having DAS28 score less than or equal to (\<=)3.2.
|
TCZ + Placebo (Pre-randomization)
n=82 participants at risk
Participants received TCZ 8 mg/kg (maximum 800 mg) via IV infusion q4w up to Week 16 (total of 4 infusions). Participants also received MTX capsules, orally at a stable dose (10, 15, 17.5, or 20 mg/week but no maximum dose was set) weekly, up to Week 16. Participants with a response were randomized to receive TCZ and matching MTX placebo in the second part of the study. Response was defined as participants having DAS28 score \<=3.2.
|
TCZ + MTX (Post-randomization)
n=83 participants at risk
TCZ 8 mg/kg (maximum 800 mg) q4w via IV infusion up to Week 16 (total of 4 infusions). Participants also received MTX capsules, orally, at a stable dose (10, 15, 17.5, or 20 mg/week but no maximum dose was set) weekly, up to Week 16. Participants with a response were randomized to receive 3 additional IV infusions of TCZ 8 mg/kg between Week 16 and Week 24 and MTX capsules, orally, at a stable dose (10, 15, 17.5, or 20 mg per week, but no maximum dose was set), weekly through Week 24. Response was defined as participants having DAS28 score \<=3.2.
|
TCZ + Placebo (Post-randomization)
n=82 participants at risk
TCZ 8 mg/kg (maximum 800 mg) q4w via IV infusion up to Week 16 (total of 4 infusions). Participants also received MTX capsules, orally, at a stable dose (10, 15, 17.5, or 20 mg/week but no maximum dose was set) weekly, up to Week 16. Participants with a response were randomized to receive 3 additional IV infusions of TCZ 8 mg/kg between Week 16 and Week 24 and matching placebo MTX capsules, orally, at a stable dose (10, 15, 17.5, or 20 mg per week, but no maximum dose was set), weekly through Week 24. Response was defined as participants having DAS28 score \<=3.2.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
7.3%
7/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
0.00%
0/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
3.6%
3/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
7.3%
6/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Hepatobiliary disorders
Hypertransaminasaemia
|
15.6%
15/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
14.5%
12/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
12.2%
10/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
9.6%
8/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
4.9%
4/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
3.6%
3/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
6.1%
5/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Infections and infestations
Respiratory tract infection
|
5.2%
5/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
9.4%
9/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
2.4%
2/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
7.3%
6/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
|
Blood and lymphatic system disorders
Neutropenia
|
7.3%
7/96 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/83 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
0.00%
0/82 • From Day 1 up to Week 36
The data were planned per the protocol to be reported separately for pre-randomization period and post-randomization period.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER